Can fenofibrate (Fenofiber) be taken together with statins?

From the Guidelines

Fenofibrate can be taken together with statins, but this combination requires careful medical supervision due to increased risk of muscle-related side effects, such as abnormal transaminase levels, myositis, and rhabdomyolysis. This combination is sometimes used in patients with severe mixed dyslipidemia who need aggressive lipid management. According to the most recent study 1, the risk of rhabdomyolysis is more common with higher doses of statins and renal insufficiency, and appears to be higher when statins are combined with gemfibrozil compared to fenofibrate.

Key Considerations

• Typical dosing includes fenofibrate (48-145 mg daily) and a statin (such as simvastatin), with careful consideration of the potential benefits and risks.
• Before starting this combination, baseline liver function tests and creatine kinase levels should be checked, with regular monitoring during treatment.
• Patients should be informed about potential muscle pain symptoms that warrant immediate medical attention.
• The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke compared with simvastatin alone in the ACCORD study 1, but prespecified subgroup analyses suggested possible benefit for men with both a triglyceride level ≥204 mg/dL and an HDL cholesterol level ≤34 mg/dL.

Important Factors

• The risk of muscle toxicity is higher with this combination because both fenofibrate and statins can independently cause muscle issues, and their effects may be additive.
• The expert panel of the 2013 American College of Cardiology/American Heart Association blood cholesterol guideline recommended that fenofibrate may be considered concomitantly with a low- or moderate-intensity statin only if the benefits from ASCVD risk reduction or triglyceride lowering outweigh the potential risk for adverse effects, as noted in 1.
• However, the FDA-approved product labeling recommends that the combined use of gemfibrozil with certain statins should be avoided, but fenofibrate is not explicitly contraindicated with statins, as seen in 1.

From the FDA Drug Label

Myopathy and Rhabdomyolysis: Have been reported in patients taking fenofibrate. Risks are increased during co-administration with a statin (with a significantly higher rate observed for gemfibrozil), particularly in elderly patients and patients with diabetes, renal failure, or hypothyroidism. (5.3)

Fenofibrate can be taken together with statins, but the risk of myopathy and rhabdomyolysis is increased. Key considerations include:

• Elderly patients: increased risk
• Patients with diabetes: increased risk
• Patients with renal failure: increased risk
• Patients with hypothyroidism: increased risk It is essential to monitor patients closely when co-administering fenofibrate with statins 2.

From the Research

Combination Therapy with Fenofibrate and Statins

• The combination of fenofibrate and statins may increase the risk of myopathy and rhabdomyolysis, as reported in a study published in 2008 3.
• However, another study published in 2012 found that the frequency and intensity of adverse events, including myopathy and rhabdomyolysis, were not significantly increased with the combination of fenofibrate and pravastatin compared to monotherapy with either drug 4.
• A review of the literature published in 2006 suggested that fenofibrate may be a more appropriate choice for combination therapy with statins due to its lower potential for myopathy compared to gemfibrozil 5.
• The risk of rhabdomyolysis with fenofibrate monotherapy is extremely rare, but it can occur, as reported in a case study published in 2007 6.
• An analysis of adverse event reports published in 2005 found that the use of fenofibrate in combination with statins resulted in fewer reports of rhabdomyolysis per million prescriptions dispensed compared to the use of gemfibrozil with statins 7.

Safety Considerations

• Clinicians should be aware of the potential interaction risk associated with concurrent use of statin and fenofibrate, as reported in a study published in 2008 3.
• Careful monitoring is recommended when fenofibrate is given to patients receiving statin therapy, particularly in patients with underlying coronary artery disease or other risk factors for myopathy 3, 5.
• The combination of fenofibrate and statins should be used with caution in patients with renal insufficiency, as it may increase the risk of decreased creatinine clearance, as reported in a study published in 2012 4.